In this paper, it is evidenced by the quantitative structu re-carcinogenic activity relation-ship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that thekey step of carcinogenesis induced b...In this paper, it is evidenced by the quantitative structu re-carcinogenic activity relation-ship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that thekey step of carcinogenesis induced by NNC is the cross-linking on the complementary basepair of DNA, through the bifunctional alkylation between α-carbon and another carbonwithin the same chain. The alkylation by the α-carbon atom is through the diazonium salt,but that by the atom other than the α-position is through the active ester formed from thehydroxylated metabolite of the chain. Therefore, the alkylation by the β-position of NNC,or by its γ-position under suitable conditions, of which the distances from the α-positionboth approach 2. 80-3. 00 A, would be the most favourable positions along with the α-posi-tion for the cross-linking to occur between the complementary base pairs of DNA, whichwill yield the carcinogenic activity of NNC. The above conception of bifunctional alkyla-tion can reduce the QSCAR of NNC to a reasonable structure-chemical reactivity relationshipunder the complex biological conditions, and is the successful extension of the Di-regiontheory to the carcinogenesis mechanism of the important NNC series. In the light of theabove viewpoint, for 153 NNCs including the nitrosamines and nitrosamides which havebeen tested reliably with animals, the correct discrimination ratio by quantitative patternrecognition according to carcinogenic activity indexes divided into 5 degrees comes up to ashigh as 97%.展开更多
In order to explore whether the protective function of GST-pi can prevent transformation in vitro, NIH3T3 cells and carcinogen glycidyl methacrylate (GMA) have been used in cell transformation study. NIH3T3 cells have...In order to explore whether the protective function of GST-pi can prevent transformation in vitro, NIH3T3 cells and carcinogen glycidyl methacrylate (GMA) have been used in cell transformation study. NIH3T3 cells have been transfected with GST-pi cDNA inserted retrovirus vector, pXT1, and then G418 resistant clones have been analyzed by Southern and Northern analyses. NIH3T3/pXGST clones that stably express GST-pi and control cells,展开更多
基金Project supported the National Natural Science Foundation of China.
文摘In this paper, it is evidenced by the quantitative structu re-carcinogenic activity relation-ship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that thekey step of carcinogenesis induced by NNC is the cross-linking on the complementary basepair of DNA, through the bifunctional alkylation between α-carbon and another carbonwithin the same chain. The alkylation by the α-carbon atom is through the diazonium salt,but that by the atom other than the α-position is through the active ester formed from thehydroxylated metabolite of the chain. Therefore, the alkylation by the β-position of NNC,or by its γ-position under suitable conditions, of which the distances from the α-positionboth approach 2. 80-3. 00 A, would be the most favourable positions along with the α-posi-tion for the cross-linking to occur between the complementary base pairs of DNA, whichwill yield the carcinogenic activity of NNC. The above conception of bifunctional alkyla-tion can reduce the QSCAR of NNC to a reasonable structure-chemical reactivity relationshipunder the complex biological conditions, and is the successful extension of the Di-regiontheory to the carcinogenesis mechanism of the important NNC series. In the light of theabove viewpoint, for 153 NNCs including the nitrosamines and nitrosamides which havebeen tested reliably with animals, the correct discrimination ratio by quantitative patternrecognition according to carcinogenic activity indexes divided into 5 degrees comes up to ashigh as 97%.
文摘In order to explore whether the protective function of GST-pi can prevent transformation in vitro, NIH3T3 cells and carcinogen glycidyl methacrylate (GMA) have been used in cell transformation study. NIH3T3 cells have been transfected with GST-pi cDNA inserted retrovirus vector, pXT1, and then G418 resistant clones have been analyzed by Southern and Northern analyses. NIH3T3/pXGST clones that stably express GST-pi and control cells,
